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Biomedical subjects

O K Andersen

Publications and source records attributed to O K Andersen.

66 records · Page 4Linked to original sources

Increased plasma levels of vasoactive intestinal polypeptide in pigs during endotoxinaemia.

Vasoactive intestinal polypeptide (VIP) is a highly potent vasodilatator. Cardiovascular changes and plasma VIP levels were studied during endotoxinaemia (Escherichia coli endotoxin 1 mg/kg) in a carefully monitored porcine model. Endotoxin infusion resulted in a profound but reversible shock and a substantial rise in plasma VIP levels. Increased levels of VIP could be demonstrated already after 30 min of endotoxin infusion and increased further during the infusion. Animals followed for a period of 60 h demonstrated slowly declining levels of VIP after endotoxin infusion but significantly elevated levels were usually found 24 h after infusion. Control animals did not show any changes in VIP during a similar procedure. Release of gastrointestinal peptides may be of importance during septic shock.

Animals↗

Effects of mechlorethamine on lysosomal enzyme release from HeLa and 3T3 cells.

The growth of the established malignant HeLa cells was much more inhibited by mechlorethamine (HN2) than that of the nonmalignant 3T3 cells. An initial growth inhibition was followed by complete inhibition even if HN2 was removed from the culture medium. Significant cell death did not occur during the first 24 h of HN2 treatment, but well later on. Incubation with 2.5 micrograms/ml HN2 caused increased release of lysosomal enzymes into the medium and decreased intracellular enzyme activities after a latency period of at least 6 h. The lysosomes from HeLa cells did not seem to be more fragile than those from 3T3 cells. Incubation with 0.25 micrograms/ml HN2 did not alter the intra- or extracellular enzyme levels the first 24 h, but well later on even after refeeding with medium without HN2. This study indicates that lysosomal enzymes are not involved in the genesis of the process leading to cell inactivation by HN2, but may well be correlated with the cytotoxic effects leading to cell death.

Cell Division↗

Tissue thromboplastin generation in circulating mononuclear phagocytes and development of coagulation disorders during E. coli endotoxinaemia in pigs.

Tissue thromboplastin generation in monocytes was studied during various stages of Escherichia coli endotoxinaemia in pigs. The pigs were monitored in halothane anaesthesia and mechanically ventilated. Blood was sampled from the superior caval vein before and during endotoxin infusion and up to 6 hours after its start. Monnuclear leukocytes were harvested with Lymphoprep separation and monocyte counts were made, using TRITC-labelled sheep erythrocytes, acridine orange and a fluorescence microscope. Thromboplastin was quantified in a two-stage assay by incubating the test sample together with purified factor X, factor VII and Ca++. The generated factor Xa was thereafter assayed. There was statistically significant increase of tissue thromboplastin activity in monocytes after endotoxin infusion. Maximum level was reached at the end of the infusion and was maintained throughout the observation period. Decrease occurred in platelets, leukocytes, antithrombin III, fibrinogen and clotting factors V, VII and VIII, and clotting time was prolonged. These findings indicated significant disseminated intravascular coagulation. The endotoxin-stimulated monocytes with their elevated tissue thrombo-plastin activity thus may play an important part in development of the DIC which so often follows septicemia.

Animals↗

Lysosomal hydrolases in neutrophils, mononuclear cells and serum during Escherichia coli endotoxinaemia in pigs.

The appearance of 10 different lysosomal enzymes in leucocytes and serum were studied during various stages of Escherichia coli endotoxinaemia in pigs. The animals were monitored in halothane anaesthesia and ventilated with a mechanical ventilator. The endotoxin infusion induced a marked increase in pulmonary artery pressure while the systemic blood pressure was significantly lowered. A pronounced decline in circulating leucocytes occurred. There was a general trend of intracellular reduction of lysosomal enzymes in both PMN and mononuclear cells, whereas increasing serum levels of the same enzymes occurred. Significantly higher serum levels of all lysosomal enzymes were found 5 h after start of endotoxin infusion compared to preinfusion values, while a significant acidosis in the aorta blood was registered. These results indicate that lysosomal enzymes are released from white blood cells following endotoxin stimulation. When local pH values allow enzyme activity, they may contribute to the tissue destruction seen in endotoxinaemia.

Animals↗

Doxepin in the treatment of duodenal ulcer. A double-blind clinical study comparing doxepin and placebo.

In the double-blind study of 51 patients with duodenal ulcer the effect of doxepin and placebo was evaluated. Complete healing of the ulcer was found in 19 of 23 patients after 4 weeks of treatment with 50 mg doxepin (83%) and in 14 of 27 patients given placebo (52%) (p less than 0.05). Two patients in the placebo group developed complications necessitating surgical intervention. No serious side effects were registered in the doxepin group.

Adult↗

Effect of doxepin on gastric secretion in man.

The effect of doxepin, a tricyclic antidepressive agent, on gastric secretion of acid and pepsin was studied in five healthy students. Dose-response studies were carried out on different days with increasing doses of doxepin on a constant background stimulation with pentagastrin and with increasing doses of pentagastrin in combination with a constant dose of doxepin. Doxepin reduced gastric acid secretion when serum values of doxepin were above 60 nmol/l.

Adult↗

Controlled endotoxinemia in pigs. A suitable model for in vivo studies of some haemodynamic, humoral and cellular reactions.

To study the haemodynamic, cellular and humoral changes seen during septicemia-endotoxinemia a relatively large animal is needed. Pigs are satisfactory in size but have a tendency to develop malignant hyperthermia reaction to stress situations and certain anaesthetic agents. This problem was solved using a screening test of halothane exposure. When later used for experiments, the nonresponding pigs developed the typical hypokinetic low-flow state after endotoxin challenge seen in the advanced stage of septicemia in man. Decreased number of circulating leucocytes and platelets, increased tissue thromboplastin production in monocytes, and a significant coagulation disorder (DIC) were observed. Release of oxygen radicals and lysosomal enzymes from leucocytes could be estimated. Endotoxin levels in plasma were easily measured. This pig model of controlled endotoxinemia correlates well with some important haemodynamic, cellular and humoral reactions observed during human in vivo observations and in vitro studies. This model may thus be a valuable tool in clinical research of endotoxinemia and septicemia.

Animals↗

Prospective nonrandomized study of conventional versus laparoscopic appendectomy.

With the introduction of laparoscopic appendectomy a prospective study was started. Patients with suspected appendicitis were selected for conventional appendectomy or laparoscopy according to the preference of the surgeon on call. During a 1-year period 233 patients were included, of whom 97 underwent conventional appendectomy and 136 laparoscopy. Among the patients selected to laparoscopy, laparoscopic appendectomy was carried out in 72 cases, conventional appendectomy in 32, and only diagnostic laparoscopy in the remaining 32. Removal of a normal appendix was significantly more common in the group of patients directly selected for conventional appendectomy compared to laparoscopy (p < 0.01). The duration of the operation was shorter (p < 0.05) and the postoperative hospital stay and the convalescence longer (p < 0.05) with conventional than with laparoscopic appendectomy. Peroperative problems and minor postoperative complications were more common (p < 0.01) with laparoscopic than conventional appendectomy. However, the clinical impact of these problems were limited. The difference between the procedures regarding major complications was not significant. Laparoscopic appendectomy seems to be at least as good as conventional appendectomy. However, randomized controlled trials are needed to decide which of the procedures to recommend.

Adolescent↗

Endoluminal radiotherapy for rectal tumors.

The present study was performed to evaluate local tumor control and side effects of endoluminal radiotherapy given to patients with rectal tumors. Twelve patients with adenocarcinoma and 10 patients with villous/adenovillous adenomas were treated with curative intent from 1989 to 1995. The majority of patients were of advanced age and in poor medical condition, and had previously been found unable to undergo radical surgery or colostomy. Three patients had tumor remains following radiotherapy, they successfully received local surgery (n = 2) or an iridium implant (n = 1) as second-line treatment. Two patients (adenomas) later experienced a local relapse. No serious side effects were observed. We conclude that endoluminal radiotherapy is an efficacious option for patients with malignant or premalignant tumors in the lower rectum who are in poor medical condition.

Adenocarcinoma↗